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Long non-coding RNA LOC285194 functions as a tumor suppressor by targeting p53 in non-small cell lung cancer

机译:长非编码RNA LOC285194通过靶向p53在非小细胞肺癌中起抑癌作用

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摘要

Recently, LOC285194 has shown a potential tumor-suppressor function in several types of human cancers, but its function in non-small cell lung cancer (NSCLC) remains unknown. This study intended to investigate the biological role of LOC285194 and its clinical significance in NSCLC. LOC285194 was detected by qRT-PCR, and its correlation with clinicopathological features of NSCLC was analyzed. The expression of LOC285194 was knocked down or ectopically expressed in lung cancer cells (A549 and H1299) and tumor cell growth, migration and invasion in vitro were investigated. In addition, the interaction of LOC285194 and target proteins was assessed by RNA pulldown and RNA immunoprecipitation in vitro. The results revealed that the expression of LOC285194 was significantly lower in tumor tissues when compared with the corresponding non-tumor tissues (P<0.001). Its expression was correlated with the tumor size (P=0.027). Kaplan-Meier analysis revealed that patients with lower LOC285194 expression had worse disease-free survival and overall survival rates (P<0.05). RNA protein interaction analysis revealed that p53 was the direct binding target of LOC285194 in NSCLC. Bioinformatics analyses suggested that depletion of LOC285149 could affect its antitumor function through the KRAS/BRAF/SMEK pathway. Our findings indicated that LOC285194 was a novel non-coding prognostic indicator and contributed to tumor suppression by targeting p53 in NSCLC, suggesting that it may be a non-coding target for NSCLC gene therapy.
机译:最近,LOC285194在几种类型的人类癌症中已显示出潜在的抑癌功能,但其在非小细胞肺癌(NSCLC)中的功能仍然未知。这项研究旨在调查LOC285194的生物学作用及其在NSCLC中的临床意义。用qRT-PCR检测LOC285194,并分析其与NSCLC临床病理特征的相关性。 LOC285194的表达在肺癌细胞(A549和H1299)中被敲低或异位表达,并研究了肿瘤细胞在体外的生长,迁移和侵袭。另外,LOC285194与靶蛋白的相互作用通过体外RNA下拉和RNA免疫沉淀来评估。结果表明,与相应的非肿瘤组织相比,LOC285194在肿瘤组织中的表达明显降低(P <0.001)。其表达与肿瘤大小相关(P = 0.027)。 Kaplan-Meier分析显示,LOC285194表达较低的患者的无病生存期和总生存率较差(P <0.05)。 RNA蛋白质相互作用分析显示p53是LOC285194在NSCLC中的直接结合靶标。生物信息学分析表明,LOC285149的耗尽可能通过KRAS / BRAF / SMEK途径影响其抗肿瘤功能。我们的发现表明,LOC285194是一种新型的非编码预后指标,并且通过靶向NSCLC中的p53有助于肿瘤抑制,这表明它可能是NSCLC基因治疗的非编码靶标。

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